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Changes observed in the behavioral response of land snails from exposure to parallel ac and dc magnetic fields demonstrate limited agreement with the predictions of an interaction model proposed by Lednev and the predictions of a recently proposed ion parametric resonance (IPR) model. However, the inadequate number of reported data points, particularly in a critical exposure range, prevents unambiguous application of either the Lednev or the IPR model. © 1995 Wiley-Liss, Inc. 相似文献
136.
Studies on specificity in Coccinellidae 总被引:2,自引:0,他引:2
R. L. Blackman 《The Annals of applied biology》1965,56(2):336-338
137.
Zhou XW Blackman MJ Howell SA Carruthers VB 《Molecular & cellular proteomics : MCP》2004,3(6):565-576
The transmembrane micronemal protein MIC2 and its partner M2AP comprise an adhesive complex that is required for rapid invasion of host cells by the obligate intracellular parasite Toxoplasma gondii. Recent studies have shown that the MIC2/M2AP complex undergoes extensive proteolytic processing on the parasite surface during invasion, including primary processing of M2AP by unknown proteases and proteolytic shedding of the complex by an anonymous protease called MPP1. While it was shown that MPP1-mediated cleavage is necessary for efficient invasion, it remained unclear whether the adhesive complex was liberated by juxtamembrane or intramembrane proteolysis. Here, using a three-phase strategy of assigning cleavage sites based on intact matrix-assisted laser desorption/ionization mass followed by confirmation by enzymatic digestion and inhibitor profiling, we demonstrate that M2AP is processed by two parasite-derived proteases called MPP2 and MPP3. We also define the substrate repertoire of MPP2 by two-dimensional differential gel electrophoresis using fluorescent tags. Finally, we use complementary mass spectrometric techniques to unequivocally show that MIC2 is shed by intramembrane cleavage within its anchoring domain. Based on the properties of this cleavage site, we conclude that the sheddase, MPP1, is likely a multipass membrane protease of the Rhomboid family. Our data support a novel two-step proteolysis model that includes primary processing of the MIC2/M2AP complex followed by secondary cleavage to shed the complex from the parasite surface during the final steps of invasion. 相似文献
138.
A multifunctional serine protease primes the malaria parasite for red blood cell invasion 总被引:1,自引:0,他引:1 下载免费PDF全文
Konstantinos Koussis Chrislaine Withers-Martinez Sharon Yeoh Matthew Child Fiona Hackett Ellen Knuepfer Luiz Juliano Ute Woehlbier Hermann Bujard Michael J Blackman 《The EMBO journal》2009,28(6):725-735
The malaria parasite Plasmodium falciparum replicates within an intraerythrocytic parasitophorous vacuole (PV). Rupture of the host cell allows release (egress) of daughter merozoites, which invade fresh erythrocytes. We previously showed that a subtilisin-like protease called PfSUB1 regulates egress by being discharged into the PV in the final stages of merozoite development to proteolytically modify the SERA family of papain-like proteins. Here, we report that PfSUB1 has a further role in ‘priming' the merozoite prior to invasion. The major protein complex on the merozoite surface comprises three proteins called merozoite surface protein 1 (MSP1), MSP6 and MSP7. We show that just before egress, all undergo proteolytic maturation by PfSUB1. Inhibition of PfSUB1 activity results in the accumulation of unprocessed MSPs on the merozoite surface, and erythrocyte invasion is significantly reduced. We propose that PfSUB1 is a multifunctional processing protease with an essential role in both egress of the malaria merozoite and remodelling of its surface in preparation for erythrocyte invasion. 相似文献
139.
Lili Zhang Brigitte E. Blackman Marcus D. Schonemann Tatjana Zogovic-Kapsalis Xiaoyu Pan Mary Tagliaferri Heather A. Harris Isaac Cohen Renee A. Reijo Pera Synthia H. Mellon Richard I. Weiner Dale C. Leitman 《PloS one》2010,5(7)
Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERα and ERβ on calcium oscillations in neurons derived from human (hES) and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERβ, but not ERα. The non-selective ER agonist 17β-estradiol (E2) rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERα agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT). In contrast, the selective ERβ agonists, 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN), MF101, and 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041) stimulated calcium oscillations similar to E2. The ERβ agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERβ activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERβ signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds. 相似文献
140.
Withers-Martinez C Suarez C Fulle S Kher S Penzo M Ebejer JP Koussis K Hackett F Jirgensons A Finn P Blackman MJ 《International journal for parasitology》2012,42(6):597-612
Release of the malaria merozoite from its host erythrocyte (egress) and invasion of a fresh cell are crucial steps in the life cycle of the malaria pathogen. Subtilisin-like protease 1 (SUB1) is a parasite serine protease implicated in both processes. In the most dangerous human malarial species, Plasmodium falciparum, SUB1 has previously been shown to have several parasite-derived substrates, proteolytic cleavage of which is important both for egress and maturation of the merozoite surface to enable invasion. Here we have used molecular modelling, existing knowledge of SUB1 substrates, and recombinant expression and characterisation of additional Plasmodium SUB1 orthologues, to examine the active site architecture and substrate specificity of P. falciparum SUB1 and its orthologues from the two other major human malaria pathogens Plasmodium vivax and Plasmodium knowlesi, as well as from the rodent malaria species, Plasmodium berghei. Our results reveal a number of unusual features of the SUB1 substrate binding cleft, including a requirement to interact with both prime and non-prime side residues of the substrate recognition motif. Cleavage of conserved parasite substrates is mediated by SUB1 in all parasite species examined, and the importance of this is supported by evidence for species-specific co-evolution of protease and substrates. Two peptidyl alpha-ketoamides based on an authentic PfSUB1 substrate inhibit all SUB1 orthologues examined, with inhibitory potency enhanced by the presence of a carboxyl moiety designed to introduce prime side interactions with the protease. Our findings demonstrate that it should be possible to develop 'pan-reactive' drug-like compounds that inhibit SUB1 in all three major human malaria pathogens, enabling production of broad-spectrum antimalarial drugs targeting SUB1. 相似文献